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Molecular Diagnostics for Complement and hemostasis mediated diseases

Complement deficiencies may lead to a variety of clinical diseases. For some diseases, a molecular variation is the reason for either an activation protein or a regulatory protein to function abnormally. This may lead to too much or too little complement activation, with clinical consequences. For some proteins these defects can be found rather easily using functional complement testing or investigating expression levels. However, for some proteins it is much harder to find the defect with these types of testing. In these cases molecular diagnostics can offer a solution. In addition, protein testing in a cascaded fashion is often time-consuming and expensive. Molecular analysis may in some cases be faster and cheaper. At Sanquin we offer targeted Next Generation Sequencing on the Ion Torrent platform. A combined complement/coagulation panel has been developed and validated under the ISO15189 scope. The following disease entities are covered by this panel:

Complement

Thrombotic microangiopathies (TTP/aHUS)

In many cases it may be difficult to distinguish between TTP and aHUS on basis of clinical signs. This panel provides variant analysis in the genes that are described to play a role in pathogenesis of this disease entity. We strive to provide the report within 4 weeks after receipt of the sample,

Meningitis

Recurrent bacterial meningitis may point to a complement terminal pathway deficiency. With this panel, all associated genes are screened for variants that are described to show an association with this disease. Confirmation on protein level can be performed on request.

Angioedema

Next to a variant in the C1-inhibitor gene, also patients with a variant in the genes encoding Factor XII and plasminogen may develop angioedema. In some cases, protein/functional testing will not yield aberrant results (e.g. type III angioedema). In these cases NGS may offer a solution.

Other diseases

For other diseases associated with the complement systems we provide a general NGS panel, containing relevant genes of the alternative and terminal complement pathways and complement regulators. On request, a classical pathway panel is available, that will be run in a research (non-ISO15189 accredited) setting.

Coagulation/Hemostasis

Thrombotic microangiopathies (TTP/aHUS)

In many cases it may be difficult to distinguish between TTP and aHUS on basis of clinical signs. This panel provides variant analysis in the genes that are described to play a role in pathogenesis of this disease entity. We strive to provide the report within 4 weeks after receipt of the sample.

Venous thrombosis

Many coagulation genes have been described as risk factor for venous thrombosis. In our general NGS panel, both pro- and anticoagulant genes will be tested. Confirmation on protein level can be performed on request.

Hemostasis

A bleeding tendency, especially running in families, may not always be diagnosed in the laboratory using routine coagulation testing. The NGS panel offers procoagulant and fibrinolytic genes that may explain bleeding in this setting. Confirmation on protein level can be performed on request.